This invention relates to a surgical implant for the localized application of radiation therapy, more particularly to a surgical implant intended for the prophylactic treatment or the mitigation of partial or total blockages in vessels, body ducts or other tubular body structures.
A number of medical problems are the result of overexuberant cellular proliferation in tubular body structures. A large proportion of end-stage renal disease (ESRD) patients use an implanted synthetic vascular graft to provide vascular access for dialysis treatment. Palder S R, Kirkman R L, Whittemore A D, et al., Vascular Access for Hemodialysis. Patency Rates and Results of Revision., Ann. Surg., 1995; 202: 235-239, discussed that these grafts typically fail in 14-19 months with a reported primary occlusion rate of 15-50% at one year. Bethard G A, Mechanical Versus Pharmacomechanical Thrombolysis for the Treatment of Thrombosis of Dialysis Access Grafts, Kidney Int., 1994; 45: 1401-1406, demonstrated clinically that, most graft failures result from thrombosis (80-90%); and in turn, the thrombosis is typically caused by a low flow condition, most frequently ( greater than 90%) stenosis at the graft/vein anastomosis. The stenosis is the result of an overexuberant cellular proliferation that has been observed following other vascular interventions including angioplasty and synthetic graft placement. It is this failure rate, and the attendant need to repair or replace the vascular access that generate the high costs and hospitalization rates associated with the management of the ESRD patient.
A similar intimal hyperplasia phenomenon has prevented the adoption of small diameter synthetic vascular grafts for use in coronary artery bypass surgery. Other conditions requiring treatment include the growth or regrowth of tumor tissues on or adjacent to body vessels, ducts and passageways.
To date, approaches to removing narrowings and blockages from body passageways have been both mechanical and pharmacological. Although many of these treatments are successful in the immediate goal of restoring flow through the duct or vessel, they do not always treat the underlying cause of the stenosis; and reclosure may occur after a short period. Treatments that involve various medical devices include balloon angioplasty, embolectomy, surgical excision or by-pass, clot aspiration and intravascular stent implantation. In contradistinction to the present invention, most of these interventions are typically undertaken to treat an existing stenosis and not as prophylactic or preventative treatments. As such, they present the risks of a secondary surgical procedure in addition to the risks and potential adverse reactions associated with the primary procedure.
Pharmocologic therapy includes the use of various xe2x80x9cblood-thinnersxe2x80x9d or anti-thrombotic agents. These powerful drugs are not suitable for all patients and are associated with a high risk of complication related to uncontrollable bleeding. While these drugs can often dissolve newly formed clots, they are less effective in removing established thrombus and have no impact on the overexuberant cellular proliferation (intimal hyperplasia) which may be the root cause of the stenosis.
With the acknowledged inadequacy of current stenosis and restenosis prevention techniques, the medical community has initiated experimental studies with a variety of local radiation delivery devices. It has been well established that radiation therapy is of value in mitigating exuberant cellular proliferation as in the case of cancer radiotherapy. More recent investigations have demonstrated the potential usefulness of various intravascular radiation delivery devices; however, no devices or treatments have thus far been developed specifically for the purpose of localized delivery of radiotherapy to tubular body structures by means of a circumferential wrap.
Some relevant proposed treatment means define devices that can be prepared in the form of sheets or films that are intended for use in essentially planar form. U.S. Pat. No. 4,946,435, describes a film sealed in an envelope. The device is flexible and can be conformed to provide radiation treatment to irregular contours. This patent discloses a polymeric radiation carrier film enclosed in a polymeric envelope. The patent describes a laminated structure but does not disclose use of a radiation attenuation element adjacent to the radioactive surface. Liprie describes a continuous radioactive sheet in U.S. Pat. No. 5,322,499. This device is defined to have an iridium/platinum core that is more rigid than an outer sealing coating. This soft outer cover is designed to allow the radioactive sheet to be cut into smaller sealed segments, thus creating sizes and essentially planar shapes suited for a particular application. This patent does not disclose the use of either an integral shield to protect non-targeted tissues or a radiation attenuation element to provide for a more even radiation dose gradient. In U.S. Pat. No. 5,342,283. Good describes radioactive microspheres that can be used to coat flexible substrates for use in the treatment of disease. This patent also does not disclose the use of either an integral shield to protect non-targeted tissues or a radiation attenuation element to provide for a more even radiation dose gradient. Park et al. describe a radioactive patch/film in U.S. Pat. No. 5,871,708. This device is designed to treat various kinds of cancers and dermal disease and consists of a laminated structure in which the radiation layer is not integral to the carrier film. This patent does not describe either a shield or a radiation attenuation element. None of the above mentioned patents contemplate treatment of obstructions in tubular body structures.
Some of the proposed radioactive devices were designed to provide radiation treatment as adjunctive therapy to coronary angioplasty procedures. A majority of coronary angioplasty procedures have been augmented with the placement of intravascular stents. One such device is described in U.S. Pat. No. 4,733,655 et seq. by Palmaz. These devices have improved six-month restenosis rates from nearly 40% to approximately 25%. Stents have also been placed across the graft/vein junction of failed dialysis access grafts as part of the effort to reopen the stenosed or occluded access grafts. Probably because the stent is placed across the return flow of blood at the juncture of the graft and the natural vein, success has been limited; and 50% of the stented grafts reclose within six months. Radioactive stents are currently being clinically studied as a potential improvement to non-radioactive stent placement following coronary angioplasty. The application of radioactive stents is described in U.S. Pat. No. 5,059,166. Early results seem to support use of the radioactive stents in conjunction with angioplasty, and six-month restenosis rates of less than 15% are being reported. However, radioactive stents will also physically obstruct flow in dialysis grafts.
Alternate treatment approaches for coronary artery restenosis involve the use of radioactive catheters or wires as part of the angioplasty procedure. These devices also require the use of a vascular puncture for access; but unlike the stent, do not involve permanent implantation of a device. The catheter type devices position an array of radioactive seeds or pellets at the site of the angioplasty for several minutes following the balloon angioplasty procedure. One example of a catheter type device has been described in U.S. Pat. No. 5,540,659. These devices deliver a single exposure dose; and thus present a much higher radioactivity dose rate than a stent implant that delivers radiation over a much longer time. This factor has raised radiation safety issues. Because the normal healing process following graft placement is quite different from the healing process following angioplasty it is unlikely that a one-time treatment with a catheter or wire device would be effective for use in treating graft related stenosis.
Radioactive balloon catheters, similar to those used for angioplasty have also been evaluated for the treatment of stenosis following coronary angioplasty. An example of a balloon catheter that is intended to function in this manner has been described in U.S. Pat. No. 5,302,168 et seq. Some versions of the balloons are filled with a radioactive liquid or gas and other catheters incorporate radioactive material in the wall of the balloon. These balloons can only be inflated for a few minutes at a time and some designs pose additional risks associated with the containment of the radioactive material.
Other proposed stenosis treatments involve the delivery of radioisotopes directly to the wall of the stenotic vessel. The isotopes are in gas or liquid form and are delivered to the treatment site by means of a pressurized catheter. An example of such a treatment means is provided in U.S. Pat. No. 5,873,811. This approach raises questions concerning possible contamination of the operating room and radiation exposure of the operating personnel and the patient. These treatments deliver a single dose of radiation at the time of the vascular intervention.
In yet other proposed treatment means, it has been suggested that brachytherapy seeds be placed in an array adjacent to the target tissue structure. This suggestion is an outgrowth of radiation therapy plans for treating tumors. Specifically, workers have proposed arrays of seeds in a delivery-mesh or sheet that is implanted over the area of a tumor. Examples of this approach are described in U.S. Pat. Nos. 4,754,745 and 5,030,195. Because these devices incorporate a number of discrete radiation sources, they cannot be used to deliver a relatively uniform radiation dose to tubular body structures. In addition, these devices do not provide a radiation attenuation element or an integral means for shielding non-targeted tissues from radiation.
Further, U.S. Pat. No. 5,897,573 describes a suture material with a beta radiation emitting isotope specifically intended to treat stenosis that might occur at the juncture of a synthetic vascular graft and a natural vessel. Because of the radiation source described and standard vascular suturing techniques, this device and method of treatment would only be effective as a limited treatment for intimal hyperplasia in very close proximity to the suture strand. This device and treatment strategy would also not be useful in cases where the target tissue site did not require repair by suturing.
Thus, prior to the development of the present invention there has been no wrap device designed to be placed around the external circumference of a tubular body structure for the prevention of stenosis or restenosis by: delivering a radiation dose to the local target area over an extended period of time, with limited radiation exposure to operators and non-targeted tissues, that can be implanted at the time of surgery without requiring a secondary intervention and that can be safely handled during the implant procedure. Further, the devices disclosed herein include a radiation attenuation element between the radioactive surface and the target tissue in closest proximity to this surface. This design assures a far greater spatial uniformity of radiation dose to the critical wall tissues of the passageway, duct or vessel than does an intravascular source, particularly in the common case of an eccentric lesion. Many clinicians and physiologists agree that neo-intimal hyperplasia originates from cells closer to the adventitia (i.e. further from the inner wall of the vessel). Thus, circumferential device placement would position the source closer to the origin of the unwanted cellular proliferation and, thus permit lower radioactivity levels to be effective.
The current invention comprises a wrap device that is designed to be positioned circumferentially around the outside of a segment of a body tissue structure, such as a vessel, duct or passageway that has been exposed during surgery. In a preferred embodiment, the wrap is composed of three elements assembled in a layered structure: a radiation shield element, a therapeutic element and a radiation attenuation element. The wrap delivers localized, uniform radiation for the purposes of the mitigation of cellular proliferation such as intimal hyperplasia or cancer that may result from a disease process or trauma to the wall of the structure. The wrap may also be positioned adjacent to a contiguous tissue surface as in the case of a vascular bypass graft and the epicardial coronary vessel on the surface of the heart.
The therapeutic element of the wrap is a radioactive isotope that has been preferably ion implanted on a metallic substrate. The radioactive surface of the wrap is preferably positioned adjacent a shield element so as to substantially limit the radiation exposure of surrounding non-targeted tissue structures. The shield element is preferably a metallic radiation absorber such as silver or gold or a polymer filled with barium or a similar radiation absorbent material.
The element of the wrap that is positioned adjacent the target tissue structure is preferably a radiation attenuation element. The radiation attenuation element is useful to absorb radiation and thus decrease the dose differential between cells of the target tissue that are closely proximate the radiation source of the therapeutic element and cells that are more distant. This provides a more uniform, safer delivery of the intended radiation dose throughout the thickness of the target tissue structure. The radiation attenuation element is preferably made of a bio-compatible polymer material such as polyurethane and may also extend completely around the shield, so as to enclose both the radiation shield element and the therapeutic element.
The wrap can be assembled by attaching the three elements through an adhesion or lamination process. The entire wrap is then formed in such a way as to conform to the curvature of the targeted body tissue structure. The wrap may be biased through the use of specific materials or through processing conditions to retain a generally cylindrical shape. Alternatively, the wrap may be formed in the general shape of two half-cylinders that can be positioned around a target body tissue structure such as a vessel, duct or passageway. The half-cylinders can be held in a generally cylindrical shape around the tissue segment by a fastening means such as a staple or suture placed through a tab that is provided as an integral part of the radiation attenuation material or by encircling the entire device with such shape retention means. A suture clip or staple placed through the border of the radiation attenuation element or a tab integral to the radiation attenuation element can be used to anchor the wrap to at least one portion of the target tissue structure, thus maintaining the relative positions of the wrap and the target tissue structure.
These and other features of the invention will be more fully understood by reference to the following drawings.